Elsevier

Urology

Volume 53, Issue 5, May 1999, Pages 898-902
Urology

Rapid Communication
Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer

https://doi.org/10.1016/S0090-4295(99)00061-8Get rights and content

Abstract

Objectives. To determine the hormonal (luteinizing hormone [LH] and testosterone) and biochemical (serum prostate-specific antigen [PSA]) response to withdrawal of luteinizing hormone-releasing hormone (LHRH) agonists in patients who received more than 2 years of LHRH therapy for advanced prostate cancer.

Methods. Fourteen patients with clinical Stage T3 or higher prostate cancer and no evidence of clinical or biochemical progression, who had received 2 years or more of LHRH therapy, were enrolled at the time of their scheduled 3-month depot injection. Patients underwent history, physical examination, and measurement of serum PSA, LH, and testosterone at baseline, monthly for 3 months, and then every 3 months for 1 year following LHRH withdrawal.

Results. The mean age of patients was 70.3 years (range 56 to 84). Patients previously received LHRH agonist for a mean of 38.6 months (range 25 to 82). All patients had castrate levels of testosterone (median 10.0 ng/dL) and suppressed LH levels (median 0.1 mIU/mL) at baseline. Median baseline PSA was 0.15 ng/mL. On multiple groupwise comparison, there was no significant change (compared with baseline) in LH or testosterone until 6 months after withdrawal and no change in PSA throughout the duration of the study (median PSA at 12 months 0.30 ng/mL). Despite significant increases in LH and testosterone when compared with baseline beginning at 6 months, both LH and testosterone remained markedly suppressed, with median testosterone remaining in the castrate range at both 6 and 9 months and significantly below the lower limit of normal at 12 months (median 111.0 ng/dL). Despite no statistically significant change for the entire cohort in serum PSA, a rising PSA was noted in 4 patients between 3 and 9 months, and LHRH therapy was reinitiated. The remaining patients continued to have suppressed LH and testosterone, with 4 patients remaining in the castrate range at 12 months.

Conclusions. The recovery of function of the hypothalamic-pituitary-testicular axis after prolonged LHRH administration is variable. Castrate levels of testosterone and suppressed LH may persist even up to 1 year after discontinuing LHRH. These results have significant implications regarding the interpretation of clinical trials incorporating neoadjuvant and adjuvant hormonal therapy. Further studies are needed to expand on these preliminary observations and should also address the feasibility of incorporating LHRH withdrawal into clinical practice.

Section snippets

Patients

Between April 1997 and September 1997, 14 patients actively followed up in our urology clinic were enrolled in a prospective pilot study. The study was approved by the University of Texas Southwestern Medical Center at Dallas Institutional Review Board. Patients with histologic confirmation of prostate cancer, locally advanced (T3 to T4) or metastatic (M1) disease, no evidence of clinical or biochemical progression, and who received LHRH agonist treatment for a minimum of 2 years were eligible.

Results

The mean age of patients enrolled was 70.3 years (range 56 to 84). At entry, patients had received LHRH agonist for a mean of 38.6 months (range 25 to 82). The results of serum determination of PSA, testosterone, and LH at baseline and at follow-up during the study are summarized in Table I. All patients had castrate levels of testosterone (median 10.0 ng/dL) and suppressed LH levels (median 0.1 mIU/mL) at baseline.

On multiple groupwise comparison (ANOVA), there was no significant change

Comment

LHRH agonists are a widely accepted alternative to orchiectomy or estrogen therapy in patients with prostate cancer. Although clearly shown in randomized comparative trials to reliably produce and maintain castrate levels of testosterone with repeated dosing, there is little information concerning the duration of effect after drug cessation. Reversibility with recovery of a normally functioning hypothalamic-pituitary-testicular axis is especially pertinent when these agents are used in the

Conclusions

The recovery of hypothalamic-pituitary-testosterone axis function after prolonged administration of LHRH agonist is variable in terms of extent and time-course. In a significant subset of patients, castrate levels of testosterone and LH suppression persist long after discontinuing therapy. These observations have significant implications, including economic aspects of dosage schedule and the interpretation of clinical trials incorporating neoadjuvant and adjuvant LHRH therapy. Further studies

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1

Dr. Hall is currently at the Department of Urology and Comprehensive Cancer Center, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157.

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